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INTRODUCTION: Vascular damage in Alzheimer's disease (AD) has shown conflicting findings particularly when analyzing longitudinal data. We introduce white matter hyperintensity (WMH) longitudinal morphometric analysis (WLMA) that quantifies WMH expansion as the distance from lesion voxels to a region of interest boundary. METHODS: WMH segmentation maps were derived from 270 longitudinal fluid‐attenuated inversion recovery (FLAIR) ADNI images. WLMA was performed on five data‐driven WMH patterns with distinct spatial distributions. Amyloid accumulation was evaluated with WMH expansion across the five WMH patterns. RESULTS: The preclinical group had significantly greater expansion in the posterior ventricular WM compared to controls. Amyloid significantly associated with frontal WMH expansion primarily within AD individuals. WLMA outperformed WMH volume changes for classifying AD from controls primarily in periventricular and posterior WMH. DISCUSSION: These data support the concept that localized WMH expansion continues to proliferate with amyloid accumulation throughout the entirety of the disease in distinct spatial locations. [ABSTRACT FROM AUTHOR]

Introduction: Screening potential participants in Alzheimer's disease (AD) clinical trials with amyloid positron emission tomography (PET) is often time consuming and expensive. Methods: A web‐based application was developed to model the time and financial cost of screening for AD clinical trials. Four screening approaches were compared; three approaches included an AD blood test at different stages of the screening process. Results: The traditional screening approach using only amyloid PET was the most time consuming and expensive. Incorporating an AD blood test at any point in the screening process decreased both the time and financial cost of trial enrollment. Improvements in AD blood test accuracy over currently available tests only marginally increased savings. Use of a high specificity cut‐off may improve the feasibility of screening with only an AD blood test. Discussion: Incorporating AD blood tests into screening for AD clinical trials may reduce the time and financial cost of enrollment. HIGHLIGHTS: The time and cost of enrolling participants in Alzheimer's disease (AD) clinical trials were modeled.A web‐based application was developed to enable evaluation of key parameters.AD blood tests may decrease the time and financial cost of clinical trial enrollment.Improvements in AD blood test accuracy only marginally increased savings.Use of a high specificity cut‐off may enable screening with only an AD blood test. [ABSTRACT FROM AUTHOR]

Background: The role of cerebrovascular damage in Alzheimer's Disease (AD) has resulted in inconsistent findings particularly when analyzing longitudinal data. We introduce WMH shape analysis (WSA) that quantifies white matter hyperintensity (WMH) expansion as the distance from lesion voxels to a region of interest boundary. We sought to examine the extent and spatial topography of WMH expansion with progression to AD. Method: Fluid‐Attenuated Inversion Recovery (FLAIR) images were extracted across two timepoints from ADNI. 275 longitudinal participants were classified into groups based on amyloid and cognitive status: 99 controls (CN), 42 amyloid positive cognitively stable preclinical (PC) AD, and 134 amyloid positive cognitively impaired AD individuals. WSA was performed on 5 WMH clusters (juxtacortical, anterior corona radiata, periventricular, parietal, and occipital/posterior horn). The intensity value for each cluster ROI boundary voxels reflects the Euclidean Distance from a voxel to the closest WMH voxel. The difference in distances (DD) for each timepoint provides a metric of WMH expansion. A voxel‐wise omnibus ANOVA was performed across all three groups followed by subsequent T‐tests. Additionally, we evaluated the relationship between the changes in DD maps with PET amyloid summary values, hypertension, and APOE e4 status. Result: WMH expansion was found to be significant across three groups (Fig. 1) and was primarily within two WMH clusters (p<0.05 corrected). T‐tests revealed that the AD group had significantly greater expansion in the juxtacortical cluster compared to CN but not the PC group (p<0.05 corrected). However, for the posterior horn that difference was driven by the PC with greater WMH expansion compared to either the AD or CN group (p<0.05 corrected). A significant association was observed with amyloid in the juxtacortical cluster but not with hypertension. A strong trend (p = 0.06 corrected) was observed for APOE e4 status in the juxtacortical cluster associating with more copies of the e4 allele. Conclusion: This new approach to quantifying and analyzing WMH longitudinal expansion revealed different patterns of expansion with increased AD severity. These results implicate that WMH growth associated with AD progression is spatially specific and grows in distinct ways throughout the disease process. [ABSTRACT FROM AUTHOR]

Background: Mild traumatic brain injury (mTBI) has been associated with a higher risk for developing dementia later in life. Several mechanisms have been proposed, with most relating to TBI accelerating AD‐linked pathological changes or decreasing neuronal and/or cognitive reserve. The purpose of this study was to compare AD‐linked biomarkers and measures of neuronal and cognitive functioning in AD participants with and without a history of mTBI. Method: The Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset was used to identify participants with dementia due to AD and a history of mTBI (n = 10),compared with a group of AD patients without TBI (n = 20) similar in gender, age (±5 years), education (± 3 years), and apolipoprotein ε4 status. Baseline cerebrospinal fluid (CSF)‐derived markers of amyloid and tau, and FDG PET glucose metabolism for three regions of interest (angular, temporal, and posterior cingulate), along with neuropsychological measures (i.e., Alzheimer's Disease Assessment Scale–Cognitive Subscale 13 items, Rey Verbal Learning Test, Wechsler Memory Scale Logical Memory, Trail Making Test), were compared between groups. Result: AD mTBI and control groups did not significantly differ in glucose metabolism using PET across regions often reduced in AD (p=0.53). CSF‐derived markers of amyloid formation also did not differ between the groups (p=0.76), though interestingly, there was a trend for higher phosphorylated tau (p=0.07) and total tau (0.08) markers in the mTBI group (Mptau=41.0, SD=15.0; Mttau=409.9, SD=133.7) relative to the control group (Mptau=31.5, SD=9.8; Mttau=319.5, SD=93.4). The groups were similar across neuropsychological measures (p's=0.16 – 0.90). Conclusion: A history of mTBI was not associated with greater markers of amyloid formation, lower cerebral glucose metabolism, or worse cognitive functioning in those with AD dementia. While not statistically significant, AD participants with mTBI did have a trend for higher tau levels compared to those with no history of TBI in this preliminary study. The findings may indicate a link between mTBI and greater accumulation of tau in some individuals that needs further evaluation in future studies with larger samples. [ABSTRACT FROM AUTHOR]